Current evidence indicates that morphine, related opioid alkaloids, and opioid peptides possess the ability to alter the release of endogenous neurotransmitters, hormones, and modulator autacoids in the intestine. We have established that release of 5-hydroxytryptamine (5-HT) is an important initial event in the intestinal stimulatory effects of morphine. Other endogenous mediators, such as adenosine triphosphate (ATP), substance P, and endorphin peptides may also participate in intestinal responses to morphine. The proposed research will employ appropriate pharmacological techniques to determine whether ATP or related neuromodulatory substances participate in responses to morphine and the characterize intestinal opioid receptors. In addition, the central control of intestinal motility as a possible action of endorphins will be explored in unanesthetized rats. A major goal is identification of the motor pathway of this effect of the endorphins.